The regulation of the pyruvate dehydrogenase multienzyme complex (PDC) will be studied in the isolated perfused liver and in isolated liver mitochondria. Metabolic flux through the PDC will be monitored by measuring the decarboxylation of (1-14C) pyruvate and the activation state of PDC (e.g., the percentage of PDC in its active form) will be monitored. Various nucleotides and substrates of interest will be monitored in the perfused liver under various metabolic conditions in order to ascertain possible mechanisms by which PDC may be regulated. The effects of hormonal treatment on the regulation of PDC (e.g., insulin, catecholamines and glucagon) will be monitored. The major focus of the study will be to attempt to translate the capability for regulating Pdc into what actually occurs during reasonable metabolic state changes in the liver.